Chronic stimulation of the β3-adrenergic receptor in obese mice resulted in a reduced adiposity associated with the promotion of lipolysis and the increase of non-shivering thermogenesis. It is known that the mitochondrial uncoupling protein 1 (UCP 1) in brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. UCP2 and UCP3 were recently cloned, but the effect on the UCP family (UCP1, UCP2, and UCP3) of a β3-adrenergic receptor agonist is unclear. Therefore, in this study, the effect of a β3-adrenergic receptor agonist on UCP1, UCP2, and UCP3 was investigated in BAT, white adipose tissue (WAT) and the gastrocnemius muscle of C57BL control and obese yellow KK mice administered with a β3-adrenergic receptor agonist, CL316, 243 for two weeks subcutaneously. UCP1 mRNA was found abundantly in BAT, but detected only slightly in subcutaneous and perimetric WAT and gastrocnemius muscle in both C57BL and yellow KK mice. UCP2 mRNA and UCP3 mRNA were also found in all of tissues examined in both mice. Daily injections of CL316, 243 resulted in a reduction of body weight and white pad weight, and in increases in the mRNA levels of UCP1 in BAT, WAT, and gastrocnemius muscle, UCP2 in BAT and WAT, UCP3 in BAT and perimetric WAT in both groups. These results suggest that a β3-adrenergic receptor agonist up-regulates not only UCP1 mRNA in BAT, WAT, and gastrocnemius muscle, but also UCP2 and UCP3 mRNA in BAT and WAT, and the whole UCP family may contribute to increased thermogenesis and anti-obesity action following the administration of a β3-adrenergic receptor agonist.
It is commonly accepted that the intrauterine growth restriction (IUGR) is correlated with an impairment of utero-placental blood flow. This blood flow is regulated by prostaglandins and nitric oxide (NO), which regulate vascular tone in placental villi. The factors that regulate utero-placental blood flow play different functions independently, and their functions differ according to the gestational stage. To evaluate the influence of NO and carbon monoxide (CO) on the feto-maternal circulation, we quantified endothelial NO synthase (eNOS) and heme oxygenase (HO) type 1 (HO-1) mRNAs in the placental villi. Forty-three placental samples were employed. We measured both eNOS and HO-1 mRNAs by Northern blot hybridization. The eNOS mRNA expression in the first trimester (relative intensity, 3.741±0.679, mean±SEM) was higher than that after the first trimester (0.500±0.038, p<0.0001). The HO-1 mRNA expression in the third trimester was higher than that before the third trimester (2.648±0.409 and 1.122±0.182, respectively, p<0.005). There was no difference in the expression of eNOS and HO-1 mRNAs between pregnancies with or without IUGR. Independent expression of eNOS and HO-1 mRNAs suggests that eNOS is important in placentation at early gestation, whereas HO-1 is important in maintenance of pregnancy for the term.
The effects of four weeks of climbing exercise on erythrocyte monocarboxylate transporter 1 (MCT1) content in rats were studied. The erythrocyte MCT1 content was significantly higher in the climbing group than in the sedentary group (p<0.05). Blood lactate concentration was higher (p<0.05), and the relationship between plasma and intra-erythrocyte lactate concentrations was positively correlated in the climbing group (r=0.80, p<0.001). When erythrocytes of the climbing group were separated into young and old ones, young erythrocytes is a tendency to have more MCT1 than old erythrocytes (NS). The increase in erythrocyte MCT1 content by a sustained voluntary climbing exercise may contribute to the rapid lactate delivery to liver and oxidative tissues.
Effect of administering black pepper (Piper nigrum Linn.), one of the commonly consumed spices and its active principle piperine, to high fat fed rats was studied for a period of 10 weeks. Black pepper at two different doses of 250mg/kg body weight and 500mg/kg body weight and piperine at 20mg/kg body weight were made into a coarse solution with distilled water and administered orally by intragastric intubation daily. The plasma and tissue lipid profile showed a remarkable reduction in the levels of total cholesterol (both the free and ester cholesterol fractions), free fatty acids, phospholipids and triglycerides in black pepper as well as in the piperine treated groups. Moreover, supplementation of the high fat fed rats with black pepper or piperine elevated the concentration of high density lipoprotein-cholesterol and reduced the concentrations of low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol in the plasma as compared with the levels in unsupplemented high fat fed rats. Thus dietary intake of black pepper or piperine was found to reduce the risk of atherosclerosis markedly by virtue of its hypolipidemic and antiatherogenic effects.
Quinaprilat, an angiotensin-converting enzyme (ACE) inhibitor, is commonly used for the therapy of hypertension, but the influence of ACE inhibitor for the atherogenesis has not been clear. Then we investigated the suppressive effect of ACE inhibitor on the expression of adhesion molecules and the production of cytokines which play an important role in the early development of atherosclerosis in endothelial cells (ECs). Quinaprilat treatment significantly reduced the activation of nuclear factor-κB (NF-κB), the surface expression of vascular cell adhesion molecule-1 (VCAM-1), the production of cytokines such as monocyte chemoattractant protein-1 and interleukin-6, and the number of mononuclear leukocytes adhering to ECs induced by tumor necrosis factor-α (TNF-α) and oxidized low-density lipoprotein (oxLDL). This suppressive effect was diminished by both a kinin B2 receptor antagonist and a nitric oxide synthase (NOS) inhibitor. These results indicated that quinaprilat reduced the activation of NF-κB under the stress of chemoattractants such as TNF-α and oxLDL through the increase of endothelial nitric oxide (NO) produced by activated endothelial nitric oxide synthase (eNOS) via a secondary accumulation of bradykinin in ECs. These results suggest an anti-atherogenic effect of ACE inhibitor.
We investigated the effects of catechins and ground green tea drinking on the susceptibilities of human low density lipoprotein (LDL) and plasma to the oxidation by CuSO4in vitro and ex vivo. The effects of (-)epicatechin (EC) and (-)epigallocatechin gallate (EGCg) on LDL oxidation in vitro were estimated by measuring the lag time of conjugated diene formation, lipid hydroperoxide and agarose gel electrophoretic mobility. EC and EGCg had antioxidant activities for LDL oxidation, and the antioxidant activity of EGCg to LDL oxidation was stronger than that of EC in vitro. In an ex vivo study, we investigated the effects of ground green tea drinking on LDL and plasma oxidation after the consumption of a cup of green tea (5g). Plasma total catechin contents were increased at 1 and 3h after the oral ingestion, and we detected (-)epigallocatechin (EGC), EC, EGCg and (+)catechin (CA) in plasma. The lag time of conjugated diene formation of plasma was increased in all subjects after consumption of green tea (p<0.028), but the susceptibility of LDL oxidation ex vivo was different among individual subjects. Although the β-carotene, α-tocopherol and uric acid contents in plasma did not change after green tea consumption, ascorbic acid contents in plasma increased at 3h after green tea ingestion. These findings suggest that catechins suppressed the susceptibilities of human LDL to oxidation by CuSO4in vitro and plasma oxidation ex vivo after ground green tea ingestion.
Neutrophils activation and tumor necrosis factor-α (TNF-α) induction play critical roles in aspirin-induced gastric mucosal injury. The aim of the present study was to determine whether electrolyzed alkaline water (EAW) can ameliorate aspirin-induced gastric mucosal injury in rats, and whether EAW can inhibit the increased gastric TNF-α expression associated with neutrophil accumulation and gastric epithelial cell apoptosis. EAW (pH 10.5, oxidation-reduction potential -450mW) was produced by electricity resolution of tap water with a device that used a platinum electrode. EAW was administered to rats via free drinking for 14 days. Aspirin-induced injury was produced by the intragastric administration of aspirin (200mg/kg) and HCl (0.15N, 8.0ml/kg). After 3h the animals were killed, and the gastric mucosal tissue was used for the assessment of macroscopic damage and tissue-associated myeloperoxidase (MPO) activity, the quantitation of TNF-α protein, and the assay of epithelial cell apoptosis. The expression of TNF-α mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR) 1h after aspirin administration. In the group drinking tap water, intragastric administration of acidified aspirin induced hyperemia and hemorrhagic erosions in rat stomachs. The increase in the total gastric erosive area after aspirin administration was significantly inhibited by pretreatment with EAW. The increases in MPO activity and epithelial cell apoptosis after aspirin administration were significantly inhibited by treatment with EAW. The gastric content of TNF-α increased and the expression of TNF-α mRNA was up-regulated after aspirin treatment. However, the peak TNF-α mRNA expression 1h after aspirin administration was inhibited by EAW. Based on these data, we conclude that the beneficial effects of EAW on aspirin-induced gastric mucosal injury may be attributed to its anti-inflammatory properties via inhibition of TNF-α expression.